The Different Sensitivity of Dendritic Degeneration in Hippocampal and Cortical Neurons to Estrogen Decline in Female Aging Mice

Aging is the most important risk factor for Alzheimer's disease (AD). Epidemiological studies reported that women have higher incidence of AD than men, which is associated with estrogen deficiency post menopause. The integrity of dendrites ensures normal neuronal function, and dendrite degeneration is one of the hallmarks in AD. However, the contribution of estrogen deficiency in dendritic remodeling during female aging is still unclarified. In the present study, female 18- and 22-month-old mice showed an age-dependent cognitive decline. Interestingly, female 18- and 22-month-old mice induced dendritic degeneration in both hippocampus and cortex, wherein the dendritic degeneration of hippocampal CA1 pyramidal neurons and cortical nonpyramidal neurons were more obvious in 18-month-old mice and that would not deteriorate in 22-month-old mice. The female mice after ovariectomy (OVX) 5 months induced similar changes in female 22-month-old mice indicating by cognitive decline and dendritic degeneration, however, dendritic degeneration of the hippocampal DG granular cells was less bad than that in female 22-month-old mice. Besides, estradiol (E2) level, and estrogen receptor α and β (ERα and ERβ) in hippocampus and cortex decreased in aged female and OVX mice. Importantly, E2 application rescued these changes induced by OVX. In conclusion, the female aging-induced dendritic remodeling existed regional differences, wherein hippocampal CA1 pyramidal neurons and cortical nonpyramidal neurons were the more vulnerable to onset of estrogen deficiency, while DG granular cells were more sensitive to age.

Delineation of a frequency-organized region isolated from the mouse primary auditory cortex

The primary auditory cortex (AI) is the representative recipient of information from the ears in the mammalian cortex. However, the delineation of the AI is still controversial in a mouse. Recently, it was reported, using optical imaging, that two distinct areas of the AI, located ventrally and dorsally, are activated by high-frequency tones, whereas only one area is activated by low-frequency tones. Here, we show that the dorsal high-frequency area is an independent region that is separated from the rest of the AI. We could visualize the two distinct high-frequency areas using flavoprotein fluorescence imaging, as reported previously. SMI-32 immunolabeling revealed that the dorsal region had a different cytoarchitectural pattern from the rest of the AI. Specifically, the ratio of SMI-32-positive pyramidal neurons to nonpyramidal neurons was larger in the dorsal high-frequency area than the rest of the AI. We named this new region the dorsomedial field (DM). Retrograde tracing showed that neurons projecting to the DM were localized in the rostral part of the ventral division of the medial geniculate body with a distinct frequency organization, where few neurons projected to the AI. Furthermore, the responses of the DM to ultrasonic courtship songs presented by males were significantly greater in females than in males; in contrast, there was no sex difference in response to artificial pure tones. Our findings offer a basic outline on the processing of ultrasonic vocal information on the basis of the precisely subdivided, multiple frequency-organized auditory cortex map in mice.

Theta Oscillations and Reactivity of Hippocampal Stratum Oriens Neurons

The supposition was advanced that the neuronal theta rhythmicity is the key mode of signal selection at the hippocampal level. To address this hypothesis, the experimental data on the responses of putative hippocampal interneurons of the stratum oriens CA1-CA3 to stimulation during enhanced theta rhythm and after its blockade are reviewed. Both a strong increase and a decrease of the natural theta rhythm disturbed the reactions of hippocampal neurons; during theta augmentation, the responses were masked or disappeared, and after theta blockade, they lost the ability to habituate. In both cases, two important events were broken: the resetting of the background activity and the phase-locking of theta cycles to stimulus. These data allow one to suppose that only important stimuli are normally capable to evoke these events and these stimuli are selected for recording. When the response to a significant stimulus occurs, the following theta prevents the responses to other stimuli. This probably protects the hippocampal activity from interference from irrelevant signals. Presumably, the absence of the theta deprives the hippocampus of this protection. During enhanced and persistent theta oscillations, the reset disappeared and theta bursts were generated without stimulus locking. In this state, the system is probably closed and the information cannot be recorded. During the theta blockade, the reset was too long and did not habituate. In this case, the system is open for any signals and the hippocampus loses the ability to select signal. This analysis suggests that information selection in the hippocampus may be performed with the participation of nonpyramidal neurons.

Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity.

Morphometric characteristics of Neuropeptide Y immunoreactive neurons of human cortical amygdaloid nucleus

Introduction Cortical amygdaloid nucleus belongs to the corticomedial part of the amygdaloid complex. In this nucleus there are neurons that produce neuropetide Y. This peptide has important roles in sleeping, learning, memory, gastrointestinal regulation, anxiety, epilepsy, alcoholism and depression. Material and methods We investigated morphometric characteristics (numbers of primary dendrites, longer and shorter diameters of cell bodies and maximal radius of dendritic arborization) of NPY immunoreactive neurons of human cortical amygdaloid nucleus on 6 male adult human brains, aged 46 to 77 years, by immunohistochemical avidin-biotin technique. Results Our investigation has shown that in this nucleus there is a moderate number of NPY immunoreactive neurons. 67% of found neurons were nonpyramidal, while 33% were pyramidal. Among the nonpyramidal neurons the dominant groups were multipolar neurons (41% - of which 25% were multipolar irregular, and 16% multipolar oval). Among the pyramidal neurons the dominant groups were the neurons with triangular shape of cell body (21%). All found NPY immunoreactive neurons (pyramidal and nonpyramidal altogether) had intervals of values of numbers of primary dendrites 2 to 6, longer diameters of cell bodies 13 to 38 ?m, shorter diameters of cell bodies 9 to 20 ?m and maximal radius of dendritic arborization 50 to 340 ?m. More than a half of investigated neurons (57%) had 3 primary dendrites. Discussion and conclusion The other researchers did not find such percentage of pyramidal immunoreactive neurons in this amygdaloid nucleus. If we compare our results with the results of the ather researchers we can conclude that all pyramidal NPY immunoreactive neurons found in this human amygdaloid nucleus belong to the class I of neurons, and that all nonpyramidal NPY immunoreactive neurons belong to the class II of neurons described by other researchers. We suppose that all found pyramidal neurons were projectional.

Heterogeneity of Phasic Cholinergic Signaling in Neocortical Neurons

Acetylcholine (ACh) is a neurotransmitter critical for normal cognition. Here we demonstrate heterogeneity of cholinergic signaling in neocortical neurons in the rat prefrontal, somatosensory, and visual cortex. Focal ACh application (100 μM) inhibited layer 5 pyramidal neurons in all cortical areas via activation of an apamin-sensitive SK-type calcium-activated potassium conductance. Cholinergic inhibition was most robust in prefrontal layer 5 neurons, where it relies on the same signal transduction mechanism (M1-like receptors, IP3-dependent calcium release, and SK-channels) as exists in somatosensory pyramidal neurons. Pyramidal neurons in layer 2/3 were less responsive to ACh, but substantial apamin-sensitive inhibitory responses occurred in deep layer 3 neurons of the visual cortex. ACh was only inhibitory when presented near the somata of layer 5 pyramidal neurons, where repetitive ACh applications generated discrete inhibitory events at frequencies of up to ∼0.5 Hz. Fast-spiking (FS) nonpyramidal neurons in all cortical areas were unresponsive to ACh. When applied to non-FS interneurons in layers 2/3 and 5, ACh generated mecamylamine-sensitive nicotinic responses (38% of cells), apamin-insensitive hyperpolarizing responses, with or without initial nicotinic depolarization (7% of neurons), or no response at all (55% of cells). Responses in interneurons were similar across cortical layers and regions but were correlated with cellular physiology and the expression of biochemical markers associated with different classes of nonpyramidal neurons. Finally, ACh generated nicotinic responses in all layer 1 neurons tested. These data demonstrate that phasic cholinergic input can directly inhibit projection neurons throughout the cortex while sculpting intracortical processing, especially in superficial layers.